Efficacy of Preoperative Autologous Blood Donation for Surgical Treatment of Thoracic Spinal Stenosis: A Propensity-Matched Cohort Study.

OBJECTIVE: Thoracic spinal stenosis (TSS) surgeries necessitate a substantial amount of allogeneic blood resources. However, the efficacy of preoperative autologous blood donation (PABD) in TSS surgery has not been clearly evaluated. Therefore, we aimed to evaluate the efficacy of PABD for TSS surgery. METHODS: This study is a retrospective study. Totally 397 patients who underwent TSS surgeries at our institution from January 2019 to June 2023 were included. Propensity score matching (PSM) was used to make the PABD and Non-PABD groups comparable at baseline. Regarding outcome measures, the incidence and amount of allogeneic blood transfusion, changes in postoperative hemoglobin and hematocrit levels, occurrence of postoperative complications, medical costs, drainage time, length of hospital stay, and postoperative neurological function were analyzed. The outcomes were compared between the matched PABD (n = 79) and Non-PABD (n = 79) groups. Univariate analysis methods were used for statistical analysis, including independent samples t-test, Wilcoxon rank-sum test, and chi-square test. RESULTS: The incidence of allogeneic blood transfusion (8.9% vs. 25.3%, p = 0.006) and volume of intraoperative red blood cell (RBC) transfusion (10.12 ± 54.52 vs. 122.78 ± 275.00 mL, p < 0.001) in the PABD group were significantly lower than those in the Non-PABD group. The PABD group had significantly higher average postoperative hemoglobin and hematocrit levels than the Non-PABD group at 1, 3, and 5 days after surgery (p < 0.05). Similarly, the PABD group exhibited a smaller reduction in hemoglobin and hematocrit levels compared with the Non-PABD group on 1, 3, and 5 days postoperatively. There were no significant intergroup differences in terms of transfusion-related complications, medical expenses, neurological function, length of hospital stay, or drainage time. Notably, PABD was an independent protective factor of allogeneic transfusion in the multivariate regression analysis (OR = 0.334, 95%CI = 0.051-0.966). CONCLUSIONS: PABD can effectively reduce the incidence of allogeneic blood transfusion and amount of allogeneic blood in TSS surgeries with safety. It also significantly improved the postoperative hemoglobin and hematocrit levels. Under the premise of clear indications, PABD is worth promoting for the surgical treatment of TSS.

Overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis: A case report.

RATIONALE: Anti-Myelin oligodendrocyte glycoprotein (MOG) and anti-metabotropic glutamate receptor 5 (mGluR5) double antibody positive encephalitis characterized by optic neuritis is extremely rare. We present a case of overlapping syndrome of MOG-IgG-associated disease and anti-mGluR5 encephalitis manifested as optic neuritis. PATIENT CONCERNS: A 60-year-old Chinses woman presented to the hospital with progressive vision loss and headache for 1 week. The cerebrospinal fluid examination was within the normal range. Visual evoked potentials study disclosed prolonged latency of P100 bilaterally. Fundus examination revealed indistinct boundaries of both optic discs. Her brain magnetic resonance imaging showed patchy hyperintensity in the posterior horn of the left ventricle and the left optic nerve. Her serum was positive for anti-MOG and anti-mGluR5 antibodies. DIAGNOSIS: The patient was diagnosed with overlapping syndrome of anti-MOG antibody-associated disease and anti-mGluR5 encephalitis mainly based on the clinical symptoms and further test of the antibody in serum. INTERVENTIONS AND OUTCOMES: She was subsequently subjected to empirical treatment with intravenous methylprednisolone. After discharge, she was given a tapering dose of oral prednisone, alongside mycophenolate mofetil. On outpatient follow-up, her symptoms showed no relapse after 1 month, and her condition remained stable. LESSONS: Early recognition of autoimmune encephalitis is crucial. The detection of cerebrospinal fluid and serum of autoimmune encephalitis and demyelinating diseases of the CNS, including MOG-IgG and mGluR5-IgG, should be strengthened in order to make a precise diagnosis and develop a comprehensive treatment plan in a timely manner.

Hemothorax caused by injury of musculophrenic artery after ultrasound-guided percutaneous liver biopsy: a case report.

BACKGROUND: Hemorrhage is the most common major complication after liver biopsy. Hemothorax is one type of bleeding and is very rare and dangerous. Several cases of hemothorax subsequent to liver biopsy have been documented, primarily attributed to injury of the intercostal artery or inferior phrenic artery and a few resulting from lung tissue damage; however, no previous case report of hemothorax caused by injury of musculophrenic artery after liver biopsy has been reported. CASE PRESENTATION: A 45-year-old native Chinese woman diagnosed with primary biliary cirrhosis due to long-term redness in urination and abnormal blood test indicators was admitted to our hospital for an ultrasound-guided liver biopsy to clarify pathological characteristics and disease staging. A total of 2 hours after surgery, the patient complained of discomfort in the right chest and abdomen. Ultrasound revealed an effusion in the right thorax and hemothorax was strongly suspected. The patient was immediately referred to the interventional department for digital subtraction angiography. Super-selective angiography of the right internal thoracic artery was performed which revealed significant contrast medium extravasation from the right musculophrenic artery, the terminal branch of the internal thoracic artery. Embolization was performed successfully. The vital signs of the patient were stabilized after the transarterial embolization and supportive treatment. CONCLUSION: This case draws attention to the musculophrenic artery as a potential source of hemorrhage after percutaneous liver biopsy.

Lycopene Regulates Macrophage Immune Response through the Autophagy Pathway Mediated by RIPK1.

The effects of lycopene (LP) on macrophage immune responses were evaluated in this study. Compared with the control treatment, LP treatment significantly increased cell vitality, phagocytic activity, and chemokine production in RAW264.7 cells. Additionally, compared with the control treatment, 4 µM LP treatment significantly activated autophagy, enhanced mitochondrial membrane potential, and upregulated receptor-interacting protein kinase 1 (RIPK1), while necrostatin-1 significantly reversed these effects of LP. Furthermore, compared with that in the control group, RIPK1 was significantly upregulated in the 4 µM LP and 4 µM LP + spautin-1 groups, whereas p-mTOR levels were reduced. More importantly, compared with that in the control group, p62 was significantly downregulated, and Beclin1, LC3-II, and Atg7 were upregulated in the 4 µM LP group, while spautin-1 significantly reversed these effects of LP. These results confirm that LP activates the mTOR/Beclin1/LC3/p62 autophagy signaling pathway through RIPK1, thereby enhancing the immune response of macrophages.

Study of Mechanics and Durability of Non-Spontaneous Combustion Coal Gangue Coarse-Aggregate High-Performance Concrete.

The coal gangue coarse-aggregate content in ordinary concrete should not be too large. In order to further improve the utilization rate of coal gangue coarse aggregate, this study used the principle of "strong wrapped weak" to prepare high-performance concrete. This study considered four factors, namely, water-binder (W/B) ratios, non-spontaneous combustion coal gangue (NCCG) coarse-aggregate contents, fly ash-slag mass ratios, and silica fume coating to prepare high-performance concrete. The workability, mechanical, and durability properties were studied, and the changes in the interfacial transition zone (ITZ) of concrete before and after sulfate attack and freeze-thaw cycles were analyzed based on the SEM test. The life prediction of NCCG coarse-aggregate high-performance concrete was carried out based on the grey system GM(1,1) prediction model. The results show that the NCCG coarse-aggregate contents have the greatest effect on compressive strength, sulfate resistance, and frost resistance. The W/B ratio has the greatest effect on the anti-carbonization properties. Fly ash-slag mixing can obtain better durability. Considering the effect on the design service life of high-performance concrete, NCCG coarse aggregate is used to prepare high-performance concrete in North China, and the recommended content is 60%; in the Northwest and Northeast regions, the recommended content is 45%. This study provides a basis for the preparation of high-performance concrete with NCCG coarse aggregate.

Genetic Association Analysis of Copy Number Variations for Meat Quality in Beef Cattle.

Meat quality is an economically important trait for global food production. Copy number variations (CNVs) have been previously implicated in elucidating the genetic basis of complex traits. In this article, we detected a total of 112,198 CNVs and 10,102 CNV regions (CNVRs) based on the Bovine HD SNP array. Next, we performed a CNV-based genome-wide association analysis (GWAS) of six meat quality traits and identified 12 significant CNV segments corresponding to eight candidate genes, including PCDH15, CSMD3, etc. Using region-based association analysis, we further identified six CNV segments relevant to meat quality in beef cattle. Among these, TRIM77 and TRIM64 within CNVR4 on BTA29 were detected as candidate genes for backfat thickness (BFT). Notably, we identified a 34 kb duplication for meat color (MC) which was supported by read-depth signals, and this duplication was embedded within the keratin gene family including KRT4, KRT78, and KRT79. Our findings will help to dissect the genetic architecture of meat quality traits from the aspects of CNVs, and subsequently improve the selection process in breeding programs.

Clinical characteristics of patient with GFAP-IgG: a review of 31 patients from two tertiary referral centers in China.

OBJECTIVE: This study presents a comprehensive analysis of the clinical characteristics of 31 patients exhibiting cerebrospinal fluid (CSF) and/or serum positivity for GFAP-IgG, with a specific emphasis on 24 cases demonstrating only GFAP-IgG positivity. The investigation thoroughly evaluates their clinical, radiological, and laboratory features, as well as treatment responses, with the objective of offering clinicians potential diagnostic and therapeutic approaches. METHODS: A total of 31 patients with GFAP-IgG in the CSF and/or serum were registered between August 2016 and August 2021 at the General Hospital of Ningxia Medical University and Huashan Hospital of Fudan University. We retrospectively reviewed their clinical records. RESULTS: Overall, the patients were positive with GFAP-IgG in their CSF (15/31), in serum (6/31), and both CSF and serum (10/31). Among them, two were eventually diagnosed with astroglioma and primary central nervous system lymphoma, respectively; one patient had typical multiple sclerosis; three exhibited overlapping GFAP-IgG and aquaporin-4-IgG (AQP4-IgG); and one patient was coexisting N-methyl-D-aspartate receptor IgG. The remaining 24 patients were only GFAP-IgG positive. In total, 22 out of the 24 patients had abnormal MRI outcomes, involving the brain, meninges, and spinal cord. Besides, seven of the 24 patients developed optic neuritis. The CSF protein levels positively correlated with the Expanded Disability Status Scale score (EDSSs). Significantly decreased EDSSs, modified Rankin Scale score, GFAP-IgG titer, CSF protein level, and CSF white blood cell counts were observed after immunomodulatory therapy. CONCLUSION: The clinical manifestations of GFAP-IgG exhibit a wide range of phenotypes that lack specificity. These findings emphasize the significance of not exclusively relying on the presence of antibodies to diagnose GFAP-A, but rather integrating them with the clinical phenotypes. GFAP-IgG testing enables the diagnosis of autoimmune GFAP astrocytopathy, a treatable autoimmune disease affecting the central nervous system. This condition provides opportunities for investigating innovative mechanisms of CNS autoimmunity and inflammation.

The role of the ferroptosis pathway in the regulation of polysaccharides for human health: A review.

Polysaccharides are natural polymers with ketone or aldehyde groups that are widely found in plants, animals, and microorganisms. They exhibit various biological activities and have potential development value in the food and pharmaceutical fields. Ferroptosis is a recently discovered modality that modulates cell death and has attracted considerable attention because it is considered to be involved in many pathophysiological processes. The inhibition of ferroptosis by reducing intracellular iron accumulation and lipid peroxidation may provide potential protective strategies against related pathologies. Ferroptosis is also involved in the physiological activities of polysaccharides, and its regulatory mechanism varies according to different physiological activities. However, a systematic summary on the involvement of ferroptosis in the physiological activities of polysaccharides is currently lacking. Therefore, this review systematically summarized the relationship between the physiological activities of polysaccharides and ferroptosis and focused on the regulatory mechanism of ferroptosis, with respect to the anti-cancer, anti-inflammatory, antioxidant, and immunomodulatory activities of all polysaccharides. The primary objective was to find new polysaccharide-related therapeutic breakthroughs for related diseases and to provide a reference for further research on polysaccharides-based therapeutics.

Predictive value of ultrasonic features and microscopic extrathyroidal extension in the recurrence of PTC.

PURPOSE: To determine the clinical value of ultrasonic features, especially extrathyroidal extension (ETE), in the prediction of PTC recurrence. METHOD: A total of 863 patients with PTC confirmed by pathological examinations from January 2012 to August 2018 were selected in this study, including 59 cases of recurrence. The Cox-proportional hazards regression analysis and Kaplan-Meier method were adopted to determine the relationship between the variables and recurrence free survival (RFS). RESULTS: The recurrence rate of PTC is 6.8 %. Tumor maximum diameter, margin, multifocality, microcalcifications, ETE and preoperative lymph node metastasis were valuable predictive factors in univariate survival analysis. Tumor larger than 20 mm, multifocality and lateral cervical lymph node metastasis were independent risk factors for PTC recurrence, and lymph node metastasis has the highest hazard ratio (HR). Preoperative lateral cervical lymph node metastasis was more often found in the gross and extensive ETE groups. Microscopic ETE has little value in predicting PTC recurrence and has no correlation with preoperative cervical lymph node metastasis. CONCLUSIONS: Tumor maximum diameter >20 mm, multifocality and lateral cervical lymph node metastasis were independent risk factors for PTC recurrence. Preoperative lateral cervical lymph nodes should be carefully examined when gross ETE and extensive ETE were detected. Microscopic ETE has no impact on preoperative cervical lymph node metastasis or tumor recurrence.

Preventive Mechanism of Lycopene on Intestinal Toxicity Caused by Cyclophosphamide Chemotherapy in Mice by Regulating TLR4-MyD88/TRIF-TRAF6 Signaling Pathway and Gut-Liver Axis.

Cyclophosphamide (CYC) is the first-line chemotherapy drug for cancer in clinical practice, and its intestinal toxicity seriously affects the treatment effect and prognosis of patients. Lycopene (LP) is the main pigment of ripe tomatoes and has strong antioxidant activity. However, the mechanism by which LP prevents CYC-induced intestinal injury remains unclear. The aim of this study was to investigate the mechanism of LP in preventing intestinal toxicity caused by CYC chemotherapy in mice. The results showed that LP significantly prevented spleen and thymus atrophy induced by CYC. In terms of intestinal injury, LP significantly increased the levels of superoxide dismutase (SOD), secretory immunoglobulin A (sIgA), interleukin (IL)-4, IL-12, and interferon (IFN)-γ, decreased the content of lipid oxidation (MDA), upregulated the protein expressions of toll-like receptors 4 (TLR4), myeloid differentiation factor 88 (MyD88), tumor necrosis factor receptor-associated factor 6 (TRAF6), toll/IL-1receptor domain containing adaptor protein inducing IFN-ß (TRIF), p-P38 MAPK (P38), and p-nuclear factor kappa-B (NF-κB) p65, and improved the small intestine tissue injury induced by CYC. In terms of liver injury, LP significantly increased the content of glutathione (GSH), decreased the contents of MDA, nitric oxide (NO), IL-1ß, IL-6, and tumor necrosis factor (TNF)-α, and repaired the liver tissue injury induced by CYC. Importantly, 10 mg/kg LP significantly prevented intestinal microbiota dysregulation in CYC mice. These results suggested that LP significantly prevented intestinal injury induced by CYC in mice by regulating the TLR4-MyD88/TRIF-TRAF6 signaling pathway and gut-liver axis.

Safety and efficacy of thermal ablation for cervical metastatic lymph nodes in papillary thyroid carcinoma: A systematic review and meta-analysis.

Background: To evaluate the safety and efficacy of radiofrequency ablation (RFA), microwave ablation (MWA), and laser ablation (LA) for the treatment of cervical metastatic lymph nodes (CMLNs) of papillary thyroid carcinoma (PTC). Methods: The Pubmed, EMBASE, Web of Science, and Cochrane Library databases were searched for studies on the safety and efficacy of thermal ablations (RFA, MWA, and LA) for the treatment of CMLNs of PTC until March 30, 2022. A review of 334 potential papers identified 17 eligible papers including 312 patients. Fixed-effects model or random-effects model was used to evaluate the pooled proportions of volume reduction rate (VRR), complete disappearance, and recurrence, and pooled estimates of changes in the largest diameter, volume, and serum Tg after ablation. The pooled proportions of overall and major complications were calculated. Subgroup analysis based on treatment modalities. The heterogeneity among studies was analyzed by using Q statistics and inconsistency index I2 . MINORS scale was used to evaluate the quality of the studies. Results: 17 eligible studies were finally identified, including 312 patients and 559 CMLNs. The pooled proportions of VRR, complete disappearance and recurrence of CMLNs were 91.28% [95% confidence interval (CI): 86.60-95.97%], 67.9% [95% CI: 53.1-81.1%] and 7.8% [95%CI: 3.0-14.1%], respectively. The pooled estimates of changes in the largest diameter, volume and serum Tg were 8.12 mm [95%CI: 6.78-9.46 mm], 338.75 mm3 [95%CI: 206.85 -470.65 mm3] and 5.96 ng/ml [95%CI: 3.68-8.24 ng/ml], respectively. The pooled proportions of overall and major complications were 2.9% [95%CI: 0.3-7.1%] and 0.3% [95%CI: 0-1.9%], respectively. Significant between-study heterogeneity was observed for complete disappearance (P<0.01, I2 =88.6%), VRR (P<0.001, I2 =99.9%), recurrence (P=0.02, I2 =47.76%), overall complications (P<0.02, I2 =44.8%), and changes in the largest diameter (P < 0.001, I2 =82.6%), volume (P<0.001, I2 =97.0%), and serum Tg (P < 0.001, I2 =93.7%). Subgroup analysis showed heterogeneity of the VRR among the treatment modality (I2 range: 84.4-100%). The VRR of MWA was the highest (97.97%), followed by RFA (95.57%) and LA (84.46%) (P < 0.001). Conclusion: All thermal ablations were safe and effective for the treatment of CMLNs of PTC. However, each treatment had significant heterogeneity in VRR. Compared with RFA and MWA, LA was less effective in reducing the volume of CMLNs of PTC.

Evaluating the safety and efficacy of microwave ablation in treatment of cervical metastatic lymph nodes of papillary thyroid carcinoma compared to repeat surgery.

OBJECTIVE: To evaluate the safety and efficacy of microwave ablation (MWA) versus repeat surgery for treating metastatic lymph nodes (MLNs) in papillary thyroid carcinoma (PTC). METHODS: Between July 2017 and October 2020, 67 patients were enrolled in this retrospective study. 19 and 48 patients underwent MWA and repeat surgery, respectively. The primary and secondary endpoints were recurrence-free survival and complication rates, respectively. The largest diameter, volume and volume reduction ratio (VRR) were analyzed before and after MWA. The effects of different ablation powers on the largest diameter, volume and VRR were investigated. Pre and posttreatment variables (e.g., baseline characteristics, serum thyroglobulin [Tg] levels, hospitalization time, treatment costs, recurrence-free survival and complication rates) were compared between groups. RESULTS: The largest diameter and volume postablation at each follow-up were smaller than the preablation levels (p < 0.05), except at the 1-month follow-up (p > 0.05). The largest diameter, volume, and VRR among the different ablation powers were not significantly different (p > 0.05). The mean serum Tg levels and biochemical remission rates were not significantly different between the groups (p > 0.05). Compared to reoperation, MWA had a shorter hospitalization time and lower treatment cost (p < 0.001). Total and minor complications were higher in the reoperation group (p < 0.05), but major complications were comparable (p > 0.05). The recurrence-free survival rate between groups was not significantly different (p = 0.401). The 1- and 3-year recurrence-free survival rates were comparable between the groups. CONCLUSIONS: MWA may be a safe and effective alternative to repeat surgery for treating MLNs of PTC in select patients.

The predictive value of revised diastolic dysfunction in outcomes of liver transplantation: A propensity score matching analysis.

Background: Diastolic dysfunction (DD), one of the earliest signs of cirrhotic cardiomyopathy (CCM), is included in the revised 2019 CCM criteria. Nonetheless, relevant research regarding the effects of revised DD on post-liver transplantation (LT) outcomes remains limited. Methods: This retrospective study enrolled patients who underwent LT for decompensated cirrhosis, from January 2018 to March 2021. Patients were divided into DD and non-DD groups. Clinical data were collected. Patients were followed up with, for at least 1 year post-LT; cardiovascular adverse events (AEs) and survival status were recorded. Risk factors were identified using 1:2 propensity score matching (PSM), after adjusting for confounding factors. The caliper value was set to 0.02. Results: Of 231 patients, 153 were diagnosed with DD (male, 81.8%; mean age, 51.5 ± 9.5 years). Nineteen patients with DD died within 1 year, post-LT. After PSM, 97 and 60 patients were diagnosed with and without DD, respectively. Patients with DD had longer intensive care unit (ICU) stays, higher perioperative cardiovascular AEs, and higher mortality rates than those without DD. In a multivariate analysis, interventricular septum (IVS), left atrial volume index (LAVI), and potassium levels were independent prognostic factors of perioperative cardiovascular AEs, while a decreased early diastolic mitral annular tissue velocity (e'), increased neutrophil-to-lymphocyte ratio (NLR) and tumor markers were predictors of mortality within 1 year post-LT after PSM (P < 0.05). Conclusion: Cardiac DD may contribute to perioperative cardiovascular AEs and mortality post-LT. Clinicians should be aware of decompensated cirrhosis in patients with DD.

Tumor acid microenvironment-activated self-targeting & splitting gold nanoassembly for tumor chemo-radiotherapy.

Low accumulation and penetration of nanomedicines in tumor severely reduce therapeutic efficacy. Herein, a pH-responsive gold nanoassembly is designed to overcome these problems. Polyethylene glycol linked raltitrexed (RTX, target ligand and chemotherapy drug) and two tertiary amine molecules (1-(2-aminoethyl) pyrrolidine and N, N-dibutylethylenediamine) are modified on the surface of the 6-nm gold nanoparticles by lipoic acid to form gold nanoassembly defined as Au-NNP(RTX). The Au-NNP (RTX) nanoassembly could remain at about 160 nm at the blood circulation (pH 7.4), while split into 6-nm gold nanoparticles due to tertiary amine protonation at tumor extracellular pH (pH 6.8). This pH-responsive disassembly behavior endows Au-NNP(RTX) better tumor tissue permeability through the better diffusion brought by the size reduction. Meanwhile, after disassembly, more RTXs on the surface of gold nanoparticles are exposed from the shielded state of assembly along with 2.25-fold augment of cellular uptake capability. Most importantly, the results show that Au-NNP(RTX) possesses of high tumor accumulation and effective tumor penetration, thereby enhancing the tumor chemo-radiotherapy efficiency.

Analysis and evaluation of the efficacy of ultrasound-guided microwave ablation for papillary thyroid microcarcinoma.

OBJECTIVE: The choice of the most appropriate therapeutic approach for a diagnosed papillary thyroid microcarcinoma (PTMC) remains controversial. The present study aimed to evaluate the efficacy of microwave ablation (MWA) for unifocal PTMC with a diameter of ≤0.6 cm. METHODS: A total of 63 consecutive patients with PTMC treated with MWA were studied retrospectively. MWA was performed using the hydrodissection technique and multidimensional fixed-needle principle. We analyzed the absorption of the MWA area and evaluated the prognosis over a follow-up period of 24 months. In addition, 83 patients with PTMC who underwent surgery were selected. The operating room characteristics and procedural complications of the two groups were compared. RESULTS: In the MWA group, the volume of nodules (p < 0.05) decreased from 0.04 ± 0.03 cm3 to 0.0001 ± 0.0004 cm3 at the 24-month follow-up after MWA, and the volume reduction rate (p < 0.05) was 99.43 ± 1.58%. The incidence of temporary reactive hyperplastic lymphadenectasis was higher and that of other complications was lower in the MWA group than in the surgery group. One percent of the patients in the surgery group had recurrence or metastasis, but none were detected in the MWA group. The loss of thyroid tissue volume (p < 0.001), operating room time (p < 0.001), and the mean length of hospital stay (p < 0.001) were significantly lower in the MWA group than in the surgery group. CONCLUSION: Ultrasound-guided MWA is an effective treatment strategy for unifocal PTMC with a diameter of ≤0.6 cm.

A pH-responsive Pt-based nanoradiosensitizer for enhanced radiotherapy via oxidative stress amplification.

Tumor radioresistance is a major issue in radiotherapy. To address it, a pH-responsive nanoradiosensitizer was synthesized employing a simple method. Initially, chloroplatinic acid was reduced by human serum albumin (HSA) to form HSA-wrapped Pt@HSA nanoparticles (NPs). Subsequently, cinnamicaldehyde (CA) was grafted on Pt@HSA via aldimine condensation to obtain nanoradiosensitizer Pt@HSA/CA NPs. CA would be released in tumor cells (pH = 5.5) to induce the production of reactive oxygen species, including H2O2, ˙OH, etc. The increased decomposition of H2O2 catalyzed by the NPs resulted in enhanced production of oxygen, leading to hypoxia relief of the tumor cells, which is beneficial for radiotherapy. Due to the high X-ray attenuation coefficient of Pt, Pt@HSA/CA NPs enhance the energy deposition of radiation. Cytotoxicity assay revealed that Pt@HSA/CA NPs resulted in a cell death rate of 77%, which was 24.4% higher than that of Pt@HSA NPs even under low-dose X-ray irradiation of 4 Gy. Colony formation assay demonstrated that the sensitization enhancement ratio was 1.37, indicating that Pt@HSA/CA NPs displayed remarkable radiosensitizing ability. Notably, in vivo results indicated that the NPs could increase the tumor inhibition rate to 91.2% with negligible side effects to normal tissues. These results demonstrate that Pt@HSA/CA NPs had outstanding tumor curative efficacy and hypotoxicity.

An oxidation responsive nano-radiosensitizer increases radiotherapy efficacy by remolding tumor vasculature.

As an excellent candidate material for nano-sensitizers, gold nanostructures have shown great potential in radiotherapy. Nevertheless, severe hypoxia and low accumulation of nanomedicine caused by poor perfusion at the tumor site have significantly reduced radiotherapy efficacy. Vascular normalization has gained attention owing to its ability to relieve hypoxia and increase perfusion. The synergistic therapy of tumor vascular normalization and radiotherapy has become a new option to increase anti-cancer efficacy. However, the commonly used strategy of suppressing a single growth factor to induce vascular normalization is limited by tumor compensatory effects. In this work, we developed a strategy to inhibit oxidative stress in tumors by generating chelating agents in response to hydrogen peroxide, thereby inhibiting multi-angiogenic factors simultaneously to normalize blood vessels. Concretely, sodium alginate (SA) reacted with 8-quinoline boric acid (QBA) to form SA-QBA. Then gold nanoparticles (Au NPs) were modified with SA-QBA to obtain Au@SA-QBA. The system was simple in structure and could generate 8HQ in response to H2O2in vitro to inhibit oxidative stress and reduce the expression of VEGF, bFGF, and Ang-2. In vivo, the perfusion unit (PU) increased by 78% after Au@SA-QBA treatment, and the coverage of pericytes increased by 32%, which in turn induced vascular normalization. In addition, blood routine and blood biochemical tests confirmed its good biocompatibility and 8HQ was not detected in the supernatant after homogenization of major organs. More importantly, after the synergistic treatment of vascular normalization and radiotherapy (4 Gy), the tumor growth inhibition rate was increased by 38.6% compared to the Au@SA-treated group with negligible side effects to normal tissues.

Construction of a pH/TGase "Dual Key"-Responsive Gold Nano-radiosensitizer with Liver Tumor-Targeting Ability.

The method of tumor microenvironment (TME)-responsive aggregation has become a promising approach to enhance treatment effect by improving the accumulation of nanoparticles in tumors. The enzymatic cross-linking strategy has widely attracted attention owing to its good aggregation stability and biocompatibility. However, the enzymes in nontumor tissue can also catalyze the cross-linking reaction and reduce accumulation of nanoparticles in tumor. In this work, a "dual key"-responsive strategy is utilized to construct a transglutaminase (TGase)/pH-responsive radiosensitizer (Au@TAcoGal) with specific aggregation behavior in hepatic tumor cells. Au@TAcoGal can retain its stability in blood circulation (pH 7.4) even in the presence of TGase in plasma. On reaching tumor sites, it can be endocytosed by hepatoma cells by the active targeting of phenylboronic acid (PBA) and aggregated under acidity and overexpression of TGase in cells. Due to its specific accumulation in hepatoma cells, radiotherapy can be operated under a lower dose of X-ray. The results show that the cellular accumulation of Au@TAcoGal increases by 30-70%, and the cell survival rate is less than 25% under X-ray irradiation. The antineoplastic results show that Au@TAcoGal exhibits a higher therapeutic effect, and the tumor inhibition rate can reach 84.21%.

Construction of an AuHQ nano-sensitizer for enhanced radiotherapy efficacy through remolding tumor vasculature.

As a radiotherapy sensitizer, gold-based nanomaterials can significantly enhance radiotherapy efficacy. However, the severe hypoxia and the low accumulation of nanomedicine at the tumor site caused by poor perfusion have seriously affected the effect of radiotherapy. Tumor vascular normalization has emerged as a new strategy for increasing the efficacy of radiotherapy due to its ability to relieve hypoxia and increase perfusion. However, a commonly used approach of blocking a single growth factor to induce vascular normalization is limited by the compensation effect of evasive drug resistance. In this work, we developed a strategy to simultaneously reduce the expression of multi-angiogenic growth factors by suppressing the oxidative stress effects in tumor. Herein, gold nanoparticles (Au NPs) were modified with 8-hydroxyquinoline (HQ) to obtain AuHQ. This system has a simple structure and could inhibit the production of reactive oxygen species in tumor cells by chelating iron ions, and attenuating the expression of angiopoietin-2, vascular endothelial growth factor and basic fibroblast growth factor in human umbilical vein endothelial cells. In vivo, AuHQ treatment increased pericyte coverage, modulated tumor leakage while alleviating tumor hypoxia and increased blood perfusion, thereby inducing tumor vascular normalization. Consequently, Au accumulation of the AuHQ group increased by 1.94 fold compared to that in the control group. Furthermore, the antitumor efficacy of radiotherapy was increased by 38% compared to the Au NPs-treated group. Therefore, AuHQ may be a promising nanomedicine for future cancer treatment.

Gastrointestinal-type chemotherapy prolongs survival in an atypical primary ovarian mucinous carcinoma: A case report.

BACKGROUND: Primary ovarian mucinous carcinoma is a rare histologic subtype of epithelial ovarian carcinoma and exhibits considerable morphologic overlap with secondary tumour. It is hard to differentiate primary from metastatic ovarian mucinous carcinoma by morphological and immunohistochemical features. Because of the histologic similarity between primary ovarian mucinous carcinoma and metastatic gastrointestinal carcinoma, it has been hypothesized that ovarian mucinous carcinomas might respond better to non-gynecologic regimens. However, the standard treatment of advanced ovarian mucinous carcinoma has not reached a consensus. CASE SUMMARY: A 56-year-old postmenopausal woman presented with repeated pain attacks in the right lower quadrant abdomen, accompanied by diarrhoea, anorexia, and weight loss for about 3 mo. The patient initially misdiagnosed as having gastrointestinal carcinoma because of similar pathological features. Based on the physical examination, tumour markers, imaging tests, and genetic tests, the patient was clinically diagnosed with ovary mucinous adenocarcinoma. Whether gastrointestinal-type chemotherapy or gynecologic chemotherapy was a favourable choice for patients with advanced ovarian mucinous cancer had not been determined. The patient received a chemotherapy regimen based on the histologic characteristics rather than the tumour origin. The patient received nine cycles of FOLFOX and bevacizumab. This was followed by seven cycles of bevacizumab maintenance therapy for 9 mo. Satisfactory therapeutic efficacy was achieved. CONCLUSION: The genetic analysis might be used in the differential diagnosis of primary ovarian mucinous carcinoma and non-gynecologic mucinous carcinoma. Moreover, primary ovarian mucinous carcinoma patients could benefit from gastrointestinal-type chemotherapy.